Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome

Bartos, Laura M. and Quach, Stefanie and Zenatti, Valerio and Kirchleitner, Sabrina V. and Blobner, Jens and Wind-Mark, Karin and Kolabas, Zeynep Ilgin and Ulukaya, Selin and Holzgreve, Adrien and Ruf, Viktoria C. and Kunze, Lea H. and Kunte, Sebastian T. and Hoermann, Leonie and Haertel, Marlies and Park, Ha Eun and Gross, Mattes and Franzmeier, Nicolai and Zatcepin, Artem and Zounek, Adrian and Kaiser, Lena and Riemenschneider, Markus J. and Perneczky, Robert and Rauchmann, Boris-Stephan and Stoecklein, Sophia and Ziegler, Sibylle and Herms, Jochen and Ertuerk, Ali and Tonn, Joerg C. and Thon, Niklas and von Baumgarten, Louisa and Prestel, Matthias and Tahirovic, Sabina and Albert, Nathalie L. and Brendel, Matthias (2024) Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome. CLINICAL CANCER RESEARCH, 30 (20). pp. 4618-4634. ISSN 1078-0432, 1557-3265

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Abstract

Purpose: Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in the brain of patients with glioblastoma have been described. However, the impact and molecular signature of neuroinflammation distant of the primary tumor site have not yet been thoroughly elucidated.Experimental Design: We performed translocator protein (TSPO)-PET in patients with newly diagnosed glioblastoma (n = 41), astrocytoma WHO grade 2 (n = 7), and healthy controls (n = 20) and compared TSPO-PET signals of the non-lesion (i.e., contralateral) hemisphere. Back-translation into syngeneic SB28 glioblastoma mice was used to characterize Pet alterations on a cellular level. Ultimately, multiplex gene expression analyses served to profile immune cells in remote brain.Results: Our study revealed elevated TSPO-PET signals in contralateral hemispheres of patients with newly diagnosed glioblastoma compared to healthy controls. Contralateral TSPO was associated with persisting epileptic seizures and shorter overall survival independent of the tumor phenotype. Back-translation into syngeneic glioblastoma mice pinpointed myeloid cells as the predominant source of contralateral TSPO-PET signal increases and identified a complex immune signature characterized by myeloid cell activation and immunosuppression in distant brain regions.Conclusions: Neuroinflammation within the contralateral hemisphere can be detected with TSPO-PET imaging and associates with poor outcome in patients with newly diagnosed glioblastoma. The molecular signature of remote neuroinflammation promotes the evaluation of immunomodulatory strategies in patients with detrimental whole brain inflammation as reflected by high TSPO expression.

Item Type: Article
Uncontrolled Keywords: REGULATORY T-CELLS; RADIOLIGAND BINDING; PET; EXPRESSION; MACROPHAGES; DISEASE; GLIOMAS; MARKER; GROWTH; CD74;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Neuropathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 20 Aug 2025 10:01
Last Modified: 20 Aug 2025 10:01
URI: https://pred.uni-regensburg.de/id/eprint/65510

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